University of Pennsylvania Engineers Innovate Cancer Treatment from Fungus

Researchers at the University of Pennsylvania's School of Engineering and Applied Science have made a groundbreaking advancement in cancer treatment by transforming a deadly fungus into a potent cancer-fighting compound. This innovative study, published in 'Nature Chemical Biology' on June 23, 2025, reveals the potential of molecules isolated from Aspergillus flavus, a toxic fungus historically linked to deaths in archaeological excavations.

The research team, led by Dr. Sherry Gao, Presidential Penn Compact Associate Professor in Chemical and Biomolecular Engineering and Bioengineering, successfully isolated a new class of molecules known as ribosomally synthesized and post-translationally modified peptides (RiPPs). These compounds were found to exhibit significant anti-leukemic properties, competing with established FDA-approved drugs.

Dr. Gao noted, "Fungi have historically contributed to medicine, with penicillin being a prime example. Our findings indicate that there is vast potential for discovering more medicinal compounds derived from natural products."

Aspergillus flavus, notorious for its yellow spores, was long regarded as a microbial threat, particularly after a series of unexplained deaths among archaeologists who opened King Tutankhamun's tomb in the 1920s. The fungus's toxins can cause serious lung infections, especially in immunocompromised individuals. However, the recent research highlights its unexpected capability as a source of new therapeutic agents.

The study identifies four distinct asperigimycins, the compounds derived from A. flavus, which demonstrated remarkable efficacy against leukemia cells. One variant, modified with a lipid found in royal jelly, exhibited effects comparable to the standard leukemia treatments cytarabine and daunorubicin.

"Understanding the interaction between lipids and the SLC46A3 gene, which facilitates the entry of these compounds into cancer cells, opens new avenues for drug development," explained Qiuyue Nie, the paper's first author and a postdoctoral fellow in Chemical and Biomolecular Engineering.

Furthermore, the research elucidates the mechanism by which asperigimycins disrupt cell division by blocking microtubule formation, a process crucial for cancer cell proliferation. Importantly, the compounds showed minimal impact on non-cancerous cells, indicating their specificity and potential for therapeutic application.

The team aims to further explore the genetic makeup of A. flavus to uncover additional RiPPs, with hopes of advancing to animal trials and eventually human clinical testing. The implications of this research could significantly shift the landscape of cancer treatment, providing a new pathway derived from a natural source.

Dr. Gao concluded, "Nature holds a treasure trove of pharmaceutical possibilities. Our commitment as researchers is to delve deeper into these natural compounds and harness their therapeutic potential to develop improved medical solutions."

This research was conducted in collaboration with several institutions, including Rice University, the University of Pittsburgh, the University of Texas MD Anderson Cancer Center, and the University of Porto, with funding from the U.S. National Institutes of Health and other organizations. The study reflects a significant step forward in the field of biomedicine, emphasizing the transformative potential of natural resources in combating diseases such as cancer.